ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
L-DOPA impairs proteasome activity in parkinsonism through D1 dopamine receptor.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- Proteasome Dysregulation in Parkinson's Disease: Insights from Blood-Based Analyses.Molecular neurobiology · 2025Article
- Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.Journal of clinical medicine · 2021Review
- Involvement of Autophagy in Levodopa-Induced Dyskinesia.Movement disorders : official journal of the Movement Disorder Society · 2021Article
- Genes Implicated in Familial Parkinson's Disease Provide a Dual Picture of Nigral Dopaminergic Neurodegeneration with Mitochondria Taking Center Stage.International journal of molecular sciences · 2021Review
- Carnosic Acid Alleviates Levodopa-Induced Dyskinesia and Cell Death in 6-Hydroxydopamine-lesioned Rats and in SH-SY5Y Cells.Frontiers in pharmacology · 2021Article
- Cell Clearing Systems Bridging Neuro-Immunity and Synaptic Plasticity.International journal of molecular sciences · 2019Review
- Dysfunction of Cellular Proteostasis in Parkinson's Disease.Frontiers in neuroscience · 2019Review
- Inhaling xenon ameliorates l-dopa-induced dyskinesia in experimental parkinsonism.Movement disorders : official journal of the Movement Disorder Society · 2018Article
- Signal transduction in L-DOPA-induced dyskinesia: from receptor sensitization to abnormal gene expression.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia.Scientific reports · 2017Article
- Gene expression analyses identify Narp contribution in the development of L-DOPA-induced dyskinesia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Astrocytosis in parkinsonism: considering tripartite striatal synapses in physiopathology?Frontiers in aging neuroscience · 2014Article
- Overexpression of parkin in the rat nigrostriatal dopamine system protects against methamphetamine neurotoxicity.Experimental neurology · 2013Article
- Protein degradation pathways in Parkinson's disease: curse or blessing.Acta neuropathologica · 2012Review
- Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias in Parkinson's disease.Parkinson's disease · 2012Article
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant membrane localization of dopamine D(1) receptor (D1R) is associated with L-DOPA-induced dyskinesia (LID), a major complication of L-DOPA treatment in Parkinson's disease (PD). Since the proteasome plays a central role in modulating neuronal response through regulation of neurotransmitter receptor intraneuronal fate, we hypothesized that the ubiquitine-proteasome proteolytic pathway could be impaired in LID. Those LIDs are actually associated with a striatum-specific decrease in proteasome catalytic activity and accumulation of polyubiquitinated proteins in experimental rodent and monkey parkinsonism. We then demonstrated that such decreased proteasome catalytic activity (1) results from D1R activation and (2) feed-back the D1R abnormal trafficking, i.e., its exaggerated cell surface abundance. We further showed that the genetic invalidation of the E3 ubiquitin-protein ligase parkin PD gene leads to exaggerated abnormal involuntary movements compared with wild-type mice. We thus established in an unprecedented series of experimental models that impairment of the ubiquitine-proteasome system at specific nodes (E3 ligase parkin, polyubiquitination, proteasome catalytic activity) leads to the same phenomenon, i.e., aberrant behavioral response to dopamine replacement therapy in PD, highlighting the intimate interplay between dopamine receptor and proteasome activity in a nondegenerative context.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.